Mixture of higher primary aliphatic alcohols, its obtention from sugar cane wax and its pharmaceutical uses

Abstract

A mixture of higher primary aliphatic alcohols of 22 to 38 carbon atoms can be obtained by saponifying and extracting steps with organic solvents from sugar cane wax. The mixture which contains tetracosanol, hexacosanol, heptacosanol, octacosanol, nonacosanol, triacontanol, dotriacontanol and tetratriacontanol can be used for the treatment of hypercholesterolemia, and atherosclerotic complications as platelet hyperaggregabiulity, ischemia and thrombosis, and prevents drug induced gastric ulcer and improves male sexual activity.

We claim: 
     
       1. A mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms comprising 1-tetracosanol, 1-hexacosanol, 1-heptacosanol, 1-octacosanol, 1-nonacosanol, 1-triacontanol, 1-dotriacontanol and 1-tetratriacontanol having the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                 0.4-2.0%.
______________________________________
     
     
     
       2. The mixture of higher primary aliphatic alcohols according to claim 1, having by the following quantitative composition:   ______________________________________
1-tetracosanol 0.80 +/- 0.1%
1-hexacosanol  6.7 +/- 0.3%
1-heptacosanol 3.0 +/- 0.3%
1-octacosanol  65.6 +/- 3.4%
1-nonacosanol  0.7 +/- 0.1%
1-triacontanol 12.5 +/- 0.6%
1-dotriacontanol
               5.0 +/- 0.4%
1-tetratriacontanol
               0.8 +/- 0.1%.
______________________________________
     
     
     
       3. The mixture of higher primary aliphatic alcohols according to claim 1 characterized by a combination with acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20 further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers. 
     
     
       4. The mixture of higher primary aliphatic alcohols according to claim 2 further comprising acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20 further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers. 
     
     
       5. The mixture of higher primary aliphatic alcohols according to claim 3 further comprising acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       6. The mixture of higher primary aliphatic alcohols according to claim 4 further comprising acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       7. A pharmaceutical formulation comprising 0.5-15.0% weight of a mixture of alcohols constituted by the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     and further comprising as pharmaceutical excipients, appropriate fillers, agglutinants, disintegrators, and lubricants.   
     
     
       8. The pharmaceutical formulation of claim 7 in the form of tablets, capsules or granules. 
     
     
       9. The pharmaceutical formulation according to claim 7 comprising 0.5-15.0% weight of a mixture of alcohols constituted by the following quantitative composition:   ______________________________________
1-tetracosanol 0.8 +/- 0.1%
1-hexacosanol  6.7 +/- 0.3%
1-heptacosanol 3.0 +/- 0.3%
1-octacosanol  65.6 +/- 3.4%
1-nonacosanol  0.7 +/- 0.1%
1-triacontanol 12.5 +/- 0.6%
1-dotriacontanol
               5.0 +/- 0.4%
1-tetratriacontanol
                0.8 +/- 0.1%.
______________________________________
     
     
     
       10. A pharmaceutical formulation comprising the mixture of higher primary aliphatic alcohols constituted by the following quantitative compositions:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     in combination with acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20, and pharmaceutically acceptable excipients selected from the group consisting of lactose, corn starch, saccharose, magnesium stearate, microcrystalline cellulose, sodium croscarmelose gelatin, cellulose acetophthalate, titanium dioxide, talc, and polyethylene.   
     
     
       11. The pharmaceutical formulation of claim 10 in the form of tablets, capsules, microgranules, or granules. 
     
     
       12. The pharmaceutical formulation of claim 10 having acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       13. A pharmaceutical formulation comprising a mixture of higher primary aliphatic alcohols constituted by the following quantitative composition:   ______________________________________
1-tetracosanol 0.8 +/- 0.1%
1-hexacosanol  6.7 +/- 0.3%
1-heptacosanol 3.0 +/- 0.3%
1-octacosanol  65.6 +/- 3.4%
1-nonacosanol  0.7 +/- 0.1%
1-triacontanol 12.5 +/- 0.6%
1-dotriacontanol
               5.0 +/- 0.4%
1-tetratriacontanol
               0.8 +/- 0.1%
______________________________________
     further comprising acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20, and pharmaceutically acceptable excipients selected from the group consisting of lactose, corn starch, saccharose, magnesium stearate, microcrystalline cellulose, sodium croscarmelose gelatin, cellulose acetophthalate, titanium dioxide, talc, and polyethylene.   
     
     
       14. The pharmaceutical formulation of claim 13 in the form of tablets, capsules, microgranules, or granules. 
     
     
       15. The pharmaceutical formulation of claim 13, having acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       16. The pharmaceutical formulation of claim 7, wherein said appropriate fillers comprise lactose or corn starch, wherein said agglutinants comprise sucrose, talc or microcrystalline cellulose, wherein said disintegrants comprise gelatin or sodium crosscarmellose, and wherein said lubricants comprise talc or magnesium stearate. 
     
     
       17. A method of administering the pharmaceutical formulation of claim 7 to animals (including humans) comprising administering of a daily dosage of 1 to 100 mg of said mixture. 
     
     
       18. The method of claim 17 wherein said daily dosage is 5 to 20 mg. 
     
     
       19. The method of claim 17 wherein said administering is orally or parenterally. 
     
     
       20. A method for obtaining a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     comprising the steps of:   melting sugar cane wax;   saponifying said melted wax;   extracting the higher primary aliphatic alcohols.   
     
     
       21. The method of claim 20 wherein said saponification comprises a homogeneous phase, using solutions of alkaline and alkaline earth hydroxides. 
     
     
       22. Method according claim 21 wherein said hydroxides are sodium, calcium or potassium hydroxides. 
     
     
       23. The method of claim 21 wherein said extracting is a solid-liquid extraction systems using as organic solvents hydrocarbons from 6 to 9 carbon atoms, ketones from 3 to 8 carbon atoms, alcohols from 1 to 5 carbon atoms, haloforms or aromatic compounds as well as mixtures thereof. 
     
     
       24. Method according claims 23 wherein said hydrocarbons are pentane, hexane, heptane or octane. 
     
     
       25. Method according to claim 23 wherein said ketones are acetone, pentanone, methyl ethyl ketone, methyl butyl ketone and/or 3-heptanone. 
     
     
       26. Method according to claim 23 wherein said alcohols are methanol, ethanol, n-propanol, 2-propanol, n-butanol, 2-butanol, n-pentanol and terbutanol. 
     
     
       27. The method of claim 20 further comprising recrystallizing said extracted higher primary aliphatic alcohols using as organic solvents hydrocarbons from 6 to 9 carbon atoms, ketones from 3 to 8 carbon atoms, alcohols from 1 to 5 carbon atoms, haloforms or aromatic compounds as well as mixtures thereof. 
     
     
       28. Method of claim 20 wherein said haloform is dichloromethane, 1,2-dichloroethane, chloroform, tricholoro-ethane, 1,2- dicholoropropane or 1,2,3-trichloropropane. 
     
     
       29. Method according to claim 20 wherein said melting temperature of the sugar cane wax is ranged between 90° to 150° C., the hydroxide concentration is in the range of 5 to 30%, the time range of the saponification step is from 30 minutes on and the time range for the extraction step is from 1 hour to 20 hours. 
     
     
       30. Method for obtaining a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol 0.8 +/- 0.1%
1-hexacosanol  6.7 +/- 0.3%
1-heptacosanol 3.0 +/- 0.3%
1-octacosanol  65.6 +/- 3.4%
1-nonacosanol  0.7 +/- 0.1%
1-triacontanol 12.5 +/- 0.6%
1-dotriacontanol
               5.0 +/- 0.4%
1-tetratriacontanol
               0.8 +/- 0.1%
______________________________________
     comprising the steps of:   melting sugar cane wax;   saponifying said melted wax;   extracting the higher primary aliphatic alcohols.   
     
     
       31. The method of claim 30 wherein said saponifying is in a homogeneous phase, comprising solutions of alkaline and alkaline earth hydroxides. 
     
     
       32. Method according to claim 30 wherein said hydroxides are sodium, calcium or potassium hydroxides. 
     
     
       33. The method of claim 30 wherein said extracting is a solid-liquid extraction systems using as organic solvents hydrocarbons from 6 to 9 carbon atoms, ketones from 3 to 8 carbon atoms, alcohols from 1 to 5 carbon atoms, haloforms or aromatic compounds as well as mixtures thereof. 
     
     
       34. Method according claim 33 wherein said hydrocarbons are pentane, hexane, heptane or octane. 
     
     
       35. Method according to claim 33 wherein said ketones are acetone, pentanone, methyl ethyl ketone, methyl butyl ketone and/or 3-heptanone. 
     
     
       36. Method according to claim 33 wherein said alcohols are methanol, ethanol, n-propanol, 2-propanol, n-butanol, 2-butanol, n-pentanol or terbutanol. 
     
     
       37. The method of claim 30 further comprising recrystallizing said extracted higher primary aliphatic alcohols using as organic solvents hydrocarbons from 6 to 9 carbon atoms, ketones from 3 to 8 carbon atoms, alcohols from 1 to 5 carbon atoms, haloforms or aromatic compounds as well as mixtures thereof. 
     
     
       38. Method of claim 36 wherein said haloform is dichloromethane, 1,2-dichloroethane, chloroform, tricholoro-ethane, 1,2-dicholoropropane or 1,2,3-trichloropropane. 
     
     
       39. Method according to claim 30 wherein benzene, toluene, ethyl benzene, phenol or p-methyl toluene are used as aromatic solvent in the extraction step. 
     
     
       40. Method according to claim 30 wherein said melting temperature of the sugar cane wax is ranged between 90° to 150° C., the hydroxide concentration is in the range of 5 to 30%, the time range of the saponification step is from 30 minutes on and the time range for the extraction step is from 1 hour to 20 hours. 
     
     
       41. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as antiplatelet agent.   
     
     
       42. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as antithrombotic agent.   
     
     
       43. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as anti-ischemic agent.   
     
     
       44. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as protective and/or curative agent against gastric ulcer induced by drugs.   
     
     
       45. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     together with acetyl salicylic acid and further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as an antiplatelet, anti-ischemic or antithrombotic agent.   
     
     
       46. A method of using of the mixture of higher primary aliphatic alcohols according to claim 45 wherein said mixture further comprises acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20. 
     
     
       47. A method of using of the mixture of higher primary aliphatic alcohols according to claim 46 wherein said mixture further comprises acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       48. A method of using a mixture of higher primary aliphatic alcohols with the following quantitative composition:   ______________________________________
1-tetracosanol 0.8 +/- 0.1%
1-hexacosanol  6.7 +/- 0.3%
1-heptacosanol 3.0 +/- 0.3%
1-octacosanol  65.6 +/- 3.4%
1-nonacosanol  0.7 +/- 0.1%
1-triacontanol 12.5 +/- 0.6%
1-dotriacontanol
               5.0 +/- 0.4%
1-tetratriacontanol
               0.8 +/- 0.1%
______________________________________
     together with acetyl salicylic acid and further comprising excipients selected from the group consisting of agglutinants, disintegrators, lubricants, sliders or fillers as antiplatelet, anti-ischemic or antithrombotic agent.   
     
     
       49. A method of using of the mixture of higher primary aliphatic alcohols according to claim 48 wherein said mixture further comprises acetyl salicylic acid in a quantitative ratio from 20:1 to 1:20. 
     
     
       50. A method of using of the mixture of higher primary aliphatic alcohols according to claim 49 wherein said mixture further comprises acetyl salicylic acid in a quantitative ratio from 10:1 to 1:10. 
     
     
       51. A mixture of higher primary aliphatic alcohols from 24 to 34 carbon atoms characterized by the following quantitative composition:   ______________________________________
1-tetracosanol  0.5-1.0%
1-hexacosanol   5.5-8.5%
1-heptacosanol  2.0-3.5%
1-octacosanol   60.0-70.0%
1-nonacosanol   0.4-1.2%
1-triacontanol  10.0-15.0%
1-dotriacontanol
                4.0-6.0%
1-tetratriacontanol
                0.4-2.0%
______________________________________
     produced according to the method of claim 20.   
     
     
       52. The method of claim 29 wherein said hydroxide concentration is from 15 to 25% and said saponifying is from about 2 to about 5 hours.